Pancreatic islet cell hormones are all involved in a complex, integrated, regulatory unit within the islets of Langerhans where both positive and negative feedback relationships exist on the synthesis and release of each islet hormone. The proposed study intends to utilize an innovative cell separation technique, magnetophoresis, to obtain primary tissue cultures of homogenous rat pancreatic A-cells, B-cells, and D-cells. These homogenous cultures will be characterized as to cell type by immunofluorescence techniques, cell viability by metabolic and morphological evaluation and cell function by assessment of hormone secretion in reponse to secretagogues such as glucose and arginine. Glucagon, insulin and somatostatin will be investigated both individually and in combination for their effect on hormonal secretion of the homogenous primary cultures of A-cells, B-cells, and D-cells These studies will increase our understanding of the regulatory mechanisms involved in islet hormone synthesis and secretions and thereby improve our insight into the complex pathological processes of diabetes mellitus. In addition, the use of magnetic microspheres to develop an efficient procedure to isolate intact islets in high yield from pancreatic tissue will be investigated.